FDA Staff Question Pfizer Rheumatoid Arthritis Pill

Will a forthcoming Pfizer pill for rheumatoid arthritis - the first oral biologic for treating this widespread affliction - pass muster with the FDA? One can never tell from the briefing documents filed by FDA medical reviewers, but agency staffers raise several questions and take a hard look at what the drugmaker and investors are betting could become a blockbuster medicine that will help Pfizer overcome generic competition to several of its biggest selling meds.

In advance of an FDA advisory committee meeting on Wednesday, agency reviewers note several issues concerning the pill, which is called tofacitinib. Overall, the pill generated "serious safety concerns" and the 168-page briefing document (which you can peruse here) notes tofacitinib carried increased risks of serious infections and malignancies, as well as higher chance of lymphoma.

Another issued raised by FDA staffers: Although X-rays were analyzed and scored, the outcomes did not always provide clearcut evidence that tofacitinib slowed the progression of structural damage in rheumatoid arthritis patients. "One conundrum associated with the assessment of efficacy in RA is the possible dissociation between clinical and radiographic outcomes. Radiographic progression may occur in people who have very low apparent disease activity and patients with clinical disease activity may have no evidence of radiographic progression," they wrote.

Analysts were not surprised. "We expected a tough (panel) and the summary and questions reflect the FDA’s hard look at both efficacy and safety," ISI Group analyst Mark Schoenebaum writes an investor note. "A new piece of information is the increase in risk of malignancy over time in (open-label long-term extension studies), particularly lymphoma. Note that in anti-TNF labels, the risk of malignancy is a Black Box warning, though the FDA noted in its conclusion that 'other therapies for rheumatoid arthritis are available that may not have a similar malignancy risk.' ”

Pfizer is counting on its pill winning over patients who have not responded to other treatments known as TNF-inhibitors, a group of injectables that collectively generate some $13 billion. These include Humira, which is sold by Abbott Laboratories; Enbrel, which is marketed by Amgen; and Remicade, a Johnson & Johnson medicine. In fact, Pfizer estimates that 30 percent to 40 percent of rheumatoid arthritis patients fail to respond to the injectables, and Wall Street believes that, if approved, tofacitinib can generate $1.5 billion annually.

"In our view, the FDA reviewer's comments suggest likelihood of approval is extremely high (greater than 90 percent)," writes Wells Fargo Securities analyst Larry Biegelsen in an investor note. "However, FDA is questioning certain attributes of the drug, which could diminish the aura surrounding tofacitinib that its efficacy is comparable to the TNF inhibitors such as Humira."

The FDA review, he continues, is also "calling into question the overall radiographic benefit of tofacitinib at both 5mg and 10mg... and questioning the dose response of tofacitinib on signs and symptoms of rheumatoid arthritis (RA), arguing that it is fairly flat. This, together with a lack of radiographic benefit and an increased risk of serious adverse events with the 10mg dose raises the possibility FDA may decide not to approve the higher dose."

Beyond the panel meeting, though, Pfizer may have to work hard to convince doctors and payers, as well. A recent survey of 100 rheumatologists and insurers found that 55 percent of these doctors say the Pfizer pill would not replace a med they are currently prescribing. And 96 percent of the payers say tofacitinib would not replace a drug that is currently offered in their plans.

Nonetheless, 85 percent of rheumatologists and 60 percent of payers have a favorable impression of the pill. And 27 percent of the rheumatologists say they would be willing to regularly prescribe a small RA molecule, with another 46 percent reporting they would do so within the first year of availability (read more here). All of which suggests that pricing will likely become a significant factor in how Pfizer itself benefits from the drug.